CA2209301A1 - Redirection of cellular immunity by protein-tyrosine kinase chimeras - Google Patents

Redirection of cellular immunity by protein-tyrosine kinase chimeras

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Publication number
CA2209301A1
CA2209301A1 CA002209301A CA2209301A CA2209301A1 CA 2209301 A1 CA2209301 A1 CA 2209301A1 CA 002209301 A CA002209301 A CA 002209301A CA 2209301 A CA2209301 A CA 2209301A CA 2209301 A1 CA2209301 A1 CA 2209301A1
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cell
target
protein
infective agent
receptor
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CA002209301A
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French (fr)
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CA2209301C (en
Inventor
Brian Seed
Charles Romeo
Waldemar Kolanus
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General Hospital Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/13—Tumour cells, irrespective of tissue of origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/464838—Viral antigens
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70514—CD4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70535—Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Cell Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Biomedical Technology (AREA)
  • Virology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biotechnology (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. The chimeric receptor includes an extracellular portion which is capable of specifically recognizing and binding the target cell or target infective agent, and (b) an intracellular portion of a protein-tyrosine kinase which is capable of signalling the therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.

Claims (40)

1. A method of directing a cellular immune response in a mammal, said method comprising administering to said mammal an effective amount of therapeutic cells, each of said therapeutic cells expressing a membrane-bound, proteinaceous chimeric receptor, comprising (a) an intracellular portion of a protein-tyrosine kinase which is capable of signalling said therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent and (b) an extracellular portion which is capable of specifically recognizing and binding said target cell or said target infective agent, whereby each of said therapeutic cells is capable of specifically recognizing and destroying said target cell or target infective agent.
2. The method of claim 1, wherein said target cell is a host cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell.
3. The method of claim 1, wherein said protein-tyrosine kinase is a member of the Syk kinase family.
4. The method of claim 3, wherein said protein-tyrosine kinase is Syk.
5. The method of claim 4, wherein said intracellular portion includes human Syk amino acids 336-628 or porcine Syk amino acids 338-630.
6. The method of claim 1, wherein each of said therapeutic cells expresses a second membrane-bound, proteinaceous chimeric receptor, said second chimeric receptor comprising (a) an intracellular portion of a second protein-tyrosine kinase which is capable of signalling said therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent and (b) an extracellular portion which is capable of specifically recognizing and binding said target cell or said target infective agent, whereby each of said therapeutic cells is capable of specifically recognizing and destroying said target cell or target infective agent.
7. The method of claim 6, wherein one of said protein-tyrosine kinases is a member of the Syk kinase family and the other of said protein-tyrosine kinases is a member of the Src kinase family.
8. The method of claim 6, wherein one of said protein-tyrosine kinases is ZAP-70 and the other of said protein-tyrosine kinases is Fyn.
9. The method of claim 6, wherein one of said protein-tyrosine kinases is ZAP-70 and the other of said protein-tyrosine kinases is Lck.
10. The method of claims 8 or 9, wherein said ZAP-70 portion includes human ZAP-70 Tyr 369.
11. The method of claims 1 or 6, wherein said cellular response is MHC-independent.
12. The method of claims 1 or 6, wherein said therapeutic cells are selected from the group consisting of: (a) T lymphocytes; (b) cytotoxic T lymphocytes; (c) natural killer cells; (d) neutrophils; (e) granulocytes;
(f) macrophages; (g) mast cells; (h) HeLa cells; and (i) embryonic stem cells (ES).
13. The method of claim 1, wherein said target infective agent is an immunodeficiency virus.
14. The method of claim 13, wherein said extracellular portion comprises an HIV envelope-binding portion of CD4.
15. The method of claims 1 or 6, wherein said therapeutic cells further express a membrane-bound, proteinaceous chimeric receptor comprising (a) an extracellular portion which is capable of specifically recognizing and binding said target cell or said target infective agent, and (b) an intracellular portion which is derived from CD28.
16. The method of claim 1, wherein said therapeutic cells destroy said receptor-bound target cell or target infective agent by cytolysis.
17. A cell which expresses a membrane-bound, proteinaceous chimeric receptor, comprising (a) an intracellular portion of a protein-tyrosine kinase which is capable of signalling said therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent and (b) an extracellular portion which is capable of specifically recognizing and binding said target cell or said target infective agent, whereby each of said therapeutic cells is capable of specifically recognizing and destroying said target cell or target infective agent.
18. The cell of claim 17, wherein said protein-tyrosine kinase is a member of the Syk kinase family.
19. The cell of claim 18, wherein said protein-tyrosine kinase is Syk.
20. The cell of claim 19, wherein said intracellular portion includes human Syk amino acids 336-628 or porcine Syk amino acids 338-630.
21. The cell of claim 17, wherein each of said therapeutic cells expresses a second membrane-bound, proteinaceous chimeric receptor, said second chimeric receptor comprising (a) an intracellular portion of a second protein-tyrosine kinase which is capable of signalling said therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent and (b) an extracellular portion which is capable of specifically recognizing and binding said target cell or said target infective agent, whereby each of said therapeutic cells is capable of specifically recognizing and destroying a target cell or target infective agent.
22. The cell of claim 21, wherein one of said protein-tyrosine kinases is a member of the Syk kinase family and the other of said protein-tyrosine kinases is a member of the Src kinase family.
23. The cell of claim 21, wherein one of said protein-tyrosine kinases is ZAP-70 and the other of said protein-tyrosine kinases is Fyn.
24. The cell of claim 21, wherein one of said protein-tyrosine kinases is ZAP-70 and the other of said protein-tyrosine kinases is Lck.
25. The cell of claims 23 or 24, wherein said ZAP-70 portion includes human ZAP-70 Tyr 369.
26. The cell of claims 17 or 21, wherein said therapeutic cells are selected from the group consisting of: (a) T lymphocytes; (b) cytotoxic T lymphocytes; (c) natural killer cells; (d) neutrophils; (e) granulocytes;
(f) macrophages; (g) mast cells; (h) HeLa cells; and (i) embryonic stem cells (ES).
27. The cell of claim 17, wherein said target infective agent is an immunodeficiency virus.
28. The cell of claim 27, wherein said extracellular portion comprises an HIV envelope-binding portion of CD4.
29. The cell of claims 17 or 21, wherein said therapeutic cells further express a membrane-bound, proteinaceous chimeric receptor comprising (a) an extracellular portion which is capable of specifically recognizing and binding said target cell or said target infective agent, and (b) an intracellular portion which is derived from CD28.
30. The cell of claim 17, wherein said therapeutic cells destroy said receptor-bound target cell or target infective agent by cytolysis.
31. The cell of claims 17 or 21, wherein said binding is MHC-independent.
32. The cell of claims 17 or 21, wherein said extracellular portion comprises the ligand-binding portion of a receptor, the receptor-binding portion of a ligand, the antigen-binding portion of an antibody, or a functional derivative thereof.
33. A cell which expresses a membrane-bound, proteinaceous chimeric receptor comprising (a) an intracellular portion of a protein-tyrosine kinase and (b) an extracellular portion which is capable of specifically recognizing and binding a target cell or target infective agent.
34. The cell of claim 33, wherein said protein-tyrosine kinase is chosen from a member of the Syk family.
35. The cell of claim 33, wherein said protein-tyrosine kinase is chosen from a member of the Src family.
36. The cell of claim 33, wherein said protein-tyrosine kinase is chosen from Syk, ZAP-70, Fyn, and Lck.
37. DNA encoding a chimeric receptor encoding a membrane-bound, proteinaceous chimeric receptor, comprising (a) an intracellular portion of a protein-tyrosine kinase which is capable of signalling said therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent and (b) an extracellular portion which is capable of specifically recognizing and binding said target cell or said target infective agent, whereby each of said therapeutic cells is capable of specifically recognizing and destroying said target cell or target infective agent.
38. DNA encoding a membrane-bound, proteinaceous chimeric receptor comprising (a) an intracellular portion of a protein-tyrosine kinase and (b) an extracellular portion which is capable of specifically recognizing and binding a target cell or target infective agent.
39. A vector comprising the chimeric receptor DNA
of claim 37.
40. A vector comprising the chimeric receptor DNA
of claim 38.
CA2209301A 1995-02-24 1996-01-24 Redirection of cellular immunity by protein-tyrosine kinase chimeras Expired - Lifetime CA2209301C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/394,177 US5912170A (en) 1991-03-07 1995-02-24 Redirection of cellular immunity by protein-tyrosine kinase chimeras
US08/394,177 1995-02-24
PCT/US1996/001001 WO1996026265A1 (en) 1995-02-24 1996-01-24 Redirection of cellular immunity by protein-tyrosine kinase chimeras

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CA2209301A1 true CA2209301A1 (en) 1996-08-29
CA2209301C CA2209301C (en) 2010-11-23

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EP (1) EP0812352B1 (en)
JP (1) JP4170389B2 (en)
KR (1) KR100454396B1 (en)
AT (1) ATE323755T1 (en)
AU (1) AU703125C (en)
CA (1) CA2209301C (en)
CZ (1) CZ294909B6 (en)
DE (1) DE69636053T2 (en)
DK (1) DK0812352T3 (en)
ES (1) ES2258772T3 (en)
FI (1) FI121012B (en)
HU (1) HU225689B1 (en)
NO (1) NO321459B1 (en)
NZ (2) NZ501340A (en)
PT (1) PT812352E (en)
RU (1) RU2225870C2 (en)
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